The general objective of the proposed research is to elucidate the microscopic changes which occur at the active sites of multi-subunit enzymes which effectively alter the catalytic properties of these enzymes. Most of the work will center on studies with glyceraldehyde-3-phosphate dehydrogenase (GPD), isolated from yeast and B. stearothermophilus, and with the endoplasmic reticulum enzyme palmitoyl-CoA synthetase (PCS). The investigation of these enzymes will involve some "classical" physical organic techniques (structure-reactivity relationships) as well as inhibition studies. Reversible and irreversible inhibitors which are analogs of reactive intermediates (e.g., multi-substrate analogs and transition state analogs) will be used to probe the conformation changes which occur in the protein in the act of catalysis. The work with GPD will center on three areas: A) The catalytic effect of NAD, B) inhibition studies and C) mechanistic studies. Inhibition studies with PCS will be carried out to further analyze the role of subunit interactions in biochemical energy transducing systems. The properties of these multi-subunit enzymes can effectively serve as models for many of the dynamic processes in biology which are mediated and controlled through conformation changes in proteins.